-Clinical study Oral lichen planus Reticular form oj oral lichen planus. A 19-year observatwn perwd in 7J patientsfrom Skmenia M. Rode, A.A. Kansky and M . Kogoj-Rode ABSTRACT Background. 75 patients (60 of them women) with the reticular form of oral lichen planus (OLP) were under observation during a 19-year period. Methods. The patients had no complaints and were referred to the specialist by their dentist. They were studied at the Department of Clinical Oral Pathology of the Medical Center in Ljubljana. · Results. A remission of the lesions was observed in 24, intensification in 9, while in 42 the lesions persisted. During the period of observation no malignant alteration was observed. Conclusion. In well-documented cases of the reticular form of OLP the malignant transformation is rare, the differential diagnosis Between OLP and leukoplakia may be however difficult on purely clinical ground. For this reason a biopsy is suggested in such cases. Introduction Lichen planus (LP) is a relatively common disorder which affects O .5% to 1.9% of population. Approximately 20% of patients in a referral oral surge1y practice were diagnosed with oral lichen planus (OLP) (1,2). OLP is a common chronic inflammatory disease of the oral mucous membranes .It is observed on the buccal mucosa, oral vestibule, gingivae and the tongue. It has a variety of clinical appearances: reticular, papular, plaque-like, erosive, ulcerative, bullous and atrophic (3 ,4,5,6). Reticular OLP is generally characterized by lesions consisting of radiating white or grey papules in a linear, annular or retiform arrangement, forming typi- cal reticular patches , rings and streaks on the oral mu- cosa. The reticular form is the most common ancl is gene- rally asymptomatic, while the ulcerative ancl bullos forms are frequently associatecl with pain. Comparecl with skin lesions, nrncosal affections are far more chronic in nature, w ith less than 20% unclergoing com- plete remission (3). OLP is histopathologically well clefinecl, characte- rized by a T cell-clominated infiltrate in proximity to the basal celi layer of the epithelium, by epithelial basal celi clestruction ancl thickening or clisruption of the base- ment membrane (7,8,9,10). Although the etiology of OLP is very complex and tl1e pathological process remains presently obscure (11), there are inclications that it may be associatecl with stress, some systemic cliseases, drugs ancl immunologic clis- Acta Dermatoven APA Vol 9, 2000, No 4 - - - --~------ ----- - 137 Oral lichen planus orders (12). Results of numerous investigations indicate that cell-mediated mechanisms are involved in the initi- ation and progression ofthe lesions (13). It is reasonable to assume that OLP is a localized autoimmune disease. Walsh et al. suggest that modified keratinocyte surface antigens are the target for the cytotoxic celi response, whereas mast cells, antigen-presenting Langerhans cells and cytokines produced by lymphocytes and keratino- cytes play a key role in the evolving lesion (14). There is an accumulating evidence for the role of TNF-a in OLP (15). Recent studies suggest the involvement of heat shock proteins as autoantigens (15). A number of studies suggest that there is a close relationship between hepatitis C virus infection and OLP in certain groups of patients (16,17) . OLP is important since the possibility of malignant transformation is mentioned in the literature (18,19,20, 21,22), the malignant potential is stili questionable. Overexpression of the p53 gene in the OLP samples without gene mutations were reported. This may be a physiological response and may serve to protect against mutagenesis; p53 mutation appears to be an early event in the process of carcinogenesis (23) . There have been a number of mainly retrospective studies from severa! countries that show only a minimal risk of malignant transformation. In his population- based 10-1 9 year prospective study Murti et al. (19) reported its malignant transformation as 0.3%, Silverman et al. (14) reported malignant transformation in 1.2%, Holmstrup et al. (22) in 1.5%, Salem (24) in 5.6%, Voute et al. (25) in 2.7%, and Silverman et al. (26) a 2.3% rate of malignant transformation during a mean tirne of 7.5 years. Material and methods Our data on 75 patients are described and compared with those from other studies. Clinical data include age, gender, previous medica! history, medications, thera- peutic protocol and malignant association. The data on 75 patients with reticular form of oral lichen were collected from a previous survey by the Department of Clinical Oral Pathology of Medica! Centre in Ljubljana. The patients had no complaints and were directed to the specialist by their dentist who had disco- vered the lesions. From ali patients the history of the present OLP, as well as general medica! and dental histo- ries were taken. The patients were studied since 1975 and were followed through to 1994. The mean age at the initial presentation was 58.3 years with a standard deviation of 5.1 years. The age range was from 41 to 64 years. Of the 75 patients 60 (80 %) were women. Three investigators double performed the oral examinations of all lesions checking each other in daylight and using the mouth mirror. Oral reticular lichen was diagnosed and registered on a clinical basis . The score of 0-3 was 138 Figure 1: Reticular oral lichen planus: typical lesions on the buccal mucosa. recorded according to the following criteria: Score O = no lesions, normal mucosa Score 1 = white striae, less than 1 cm2 Score 2 = white striae, more than 1 cm2 Score 3 = white striae, more than 2 cm2 . Figure 2: Reticulat oral lichen planus: a more intense lesion on the buccal mucosa Clini c al s tud y Acta Dermatoven APA Vol 9, 2000, No 4 C l i n i c a l s t u d y Oral lichen planus Table 1. Lesion sites in 75 patients with oral lichen planus into other forms of OLP was not observed. Sites No. Buccal mucosa 47 Retromolare pad 15 Tongue 10 Floor of the mouth and gingiva 3 All lesions 75 Table 2. Evolution of lesions during a 19-year observation -period Situation No. Remission 24 Complete remission o Intensification 9 Status guo 42 All changes 75 From all our patients biopsies oflesional oral mucosa were removed under local anesthesia and fixed in 10% formaldehyde solution for routine histopathology. The diagnosis of OLP was confirmed histologically at the Institute of Pathology, Medica! Faculty of Ljubljana. No patient had characteristic skin lesions. Patients with lichenoid lesions close to dental amalgam fillings and patients w ith oral lichenoid drug eruptions (27) were not included in the group under obse1vation . The patients were re-examined once every six months and lesions showing clinical changes were registered. Biopsy was repeated after 10 years of obser- vation in 9 patients with a progredient OLP. They received no treatment during the years under obser- vation. Results 1. Location of the lesions The primary lesion site was the buccal mucosa, with secondary sites of the retromolar pads, tertiaty sites on the tongue and guaternary sites on the floor of the mouth and the gingiva. Multiple lesion sites occurred freguently (Table 1). 2. Lesions' evolution Disease remission was noted in 24 patients after initial presentation. A more pronounced expression of the lesions was noted in 9 patients and an unchanged situation was observed in 42 patients over a 19-year period after initial observation (Table 2). Transformation 3. Histopathologic finclings Ali tissue specimens showed similar histological abnor- malities. The epithelium of the oral mucosa was hyper- plastic with acanthotic projections, hyperplasia was seen in the spinous layer; the epithelium was coverecl by a parakeratotic layer. Liguefaction of the basal cell layer was observed focally, accompanied by marked mono- nuclear infiltrate at the dermoepiclermal junction. No atypia of the epithelial cells was found. Histopatho- logical findings after 10 years of observations were simi- lar to previous findings. No clysplasia was founcl. 4. No malignant alteration was detected in any of the 75 patients. D-iscussion The data presentecl are consistent w ith data from previous studies with regarcl to location and clisease Figure 3: Histopathology of reticular oral lichen planus: parakeratosis, acanthosis, vacuolar degeneration of basal cells, typical lichenoid lymphocytic infiltrate. H.E. x 195. Acta Dermatoven APA Vol 9, 2000, No 4 ------------------ 139 Oral lichen planus chronicity (3,14). Disease remission was noted without treatment. Female patients prevailed. The routine biopsy procedure in the diagnosis of OLP is a controversial one (3,28). From all lesions in our study biopsies were routinely taken. All tissue specimens showed similar histological abnormalities. No atypia of the epithelial cells was found. We recorded no cases of malignant transformation. Our results confirm findings of Brown et al. (3) and do not support the observations of Silverman et al. (20) who reported malignant transformation in one of the cases with reticular OLP. The results of Holmstrup et al. (29,30) who reported that reticular OLP is related to oral cancer could not be confirmed either. Reticular oral lichen planu s manifests itself with typical clinical symp- toms. There are lesions that clinically do not resemble oral lichen planus but have lichenoid features in histology, and others that clinically resemble oral lichen planus , but show atypia or dysplasia from the onset (26). This may be the source of some of the controversy in the literature concerning its malignant transformation (22), (25). No case of malignant transformation in 75 patients followed up to 19 years was recorded. We re- corded disease remission without therapy in 24 patients and intensification of mucosal striae in 9 patients. Our study does no support the observations of Brown et al. (3) or the findings of Thorn et al. (30) who suggested a complete remission. A malignant transformation of ali forms of oral lichen planus cannot be excluded. However, it would therefore REFERENCE S Figure 4: Same as figure 3. H.E. x 250. seem prudent to confirm the clinical diagnosis of OLP histologically, and to have patients followed up re- gularly. Conclusion It is suggested that a biopsy should be performed in ali instances of OLP and that the patients should be followed up regularly. l. Brown RS, Bottomley WK, Puente E, Lavigne GL. A retrospective evaluation of 193 patients with oral lichen planus. J Oral Pathol Med 1993; 22: 69-72. 2. Scully C, El - Kom M. Lichen planus: review and update on pathogenesis. J Oral Pathol 1985; 14: 431- 58. 3. Cooke BD. Keratinizing lesions affecting the oral mucosa. Proc Roy Soc Med 1967; 60: 819-22. 4. AndreasenJO. Oral lichen planus. Oral Surg Oral Med Oral Pathol 1968; 25: 31-42. 5. ThornJJ, Holmstrup P, RindumJ, Pindborg]J. Course ofvarious clinical forms of oral lichen planus. J Oral Pathol 1988; 17: 213- 8. 6. Altman J, Perry HO. Variations and course oflichen planus . Arch Dermatol 1961; 84: 179-91. 7. Walsh LJ, Savage N\V, Ishi T, Seymour GJ. Immunopathogenesis of oral lichen planus. J Oral Pathol Med 1990; 19: 389-96. 8. Silverman S, Gorsky M, Lozada-Nur F. A prospective follow - up study of 570 patients with oral lichen planus. Oral Surg Oral Med Oral Pathol 1985; 60: 30-4 . 9. Kovesi G, Banoczy J. Follow - up studies in oral lichen planus. IntJ Oral Surg 1973; 2: 13-22. 10. Silverman S, Griffith M. Studies of oral lichen planus. Oral Surg 1974; 37: 705-14. 11. Murti PR, Daftary DK, Bhonsle RB, Gupta PC, Mehta FS, Pindborg JJ. Malignant potential of oral lichen planus. J Oral Pathol 1986; 15: 71-7. Clinical stud y 140 Acta Dermatoven APA Vol 9, 2000, No 4 Clinical study AUTHORS' ADDRESSES Oral lichen planus 12. Salem G. Oral lichen planus . Comm Dent Oral Epidemiol 1989; 17: 322-4. 13. Voute ABE, De Jong WFB, Schulten EM, Snow GB, Van der Wall.Possible premalignant character of oral lichen planus. J Oral Pathol Med 1992; 21: 326-9. 14. Holmstrup P. The controversy of a premalignant potential of oral lichen planus is ove . Oral Surg Oral Med Oral Pathol 1992; 73: 704-6. 15. Barnard NA, Scully C, Everson JW, Cunningham S, Parter SR. Oral cancer development in patients with oral lichen planus. J Oral Pathol Med 1993; 22: 421-4. 16. Holmstrup P, ThornJJ, RindumJ, PindborgJJ. Malignant development oflichen planus - affected oral mucosa. J Oral Pathol 1988; 17: 219-25. 17. Silverman S, Gorsky M, Lozada-Nur F, Giannotti K. A prospective study of findings and management in 214 patients with oral lichen planu. Oral Surg Oral Med Oral Pathol 1991; 72: 665-70. Maljaž Rode DMD, PhD, Projessor oj stomatology, Department oj Oral Pathology, Medical Centre, Prvomajska 5, 1000 Ljubljana, Slovenia Andrej Kansky DMD; Msc, Department oj Maxillojacial Surgery; University Clinical Centre, Zaloška 2, 1525 Ljubljana, Slovenia Mirela Kogoj-Rode DMD, PhD, Department oj Stomatolof,y, University Glinica! Centre, Zaloška 2, 1525 Ljubljana, Slovenia Acta Dermatoven APA Vol 9, 2000, No 4 - ------------- ----141